The role of colony-stimulating factor-1 and 1,25(OH)2D3 in macrophage proliferation and polarization and their impact on the formation of calcium oxalate kidney stones

doi:10.3877/cma.j.issn.1674-3253.2026.02.013

Abstract

Abstract:

Objective

To explore the role of colony-stimulating factor-1(CSF-1) and 1,25(OH)₂D₃ in macrophage proliferation and polarization and their impact on the formation of calcium oxalate kidney stones.

Methods

Fifteen 8-week-old male CSF-1-deficient C57 mice were randomly divided into three groups: a control group, a CSF-1 induction group, and a 1,25(OH)₂D₃+CSF-1 intervention group. Bone marrow macrophages from each group of mice were cultured. Optical microscopy, flow cytometry, and quantitative real-time polymerase chain reaction were used to detect the number of macrophages and the expression levels of CD206 and CSF-1 receptor mRNA in each group.

Results

The CSF-1 group significantly increased the number of macrophages and the expression of the M2 marker CD206. Although the combined treatment with 1,25(OH)₂D₃ and CSF-1 had a synergistic effect, it was less effective than the CSF-1 induction group.

Conclusion

1,25(OH)₂D₃ and CSF-1 play significant roles in regulating macrophage proliferation and polarization towards the M2 type, and there is an interrelationship between them, which provides a new research direction for the immunomodulation of calcium oxalate kidney stones.

Key words: CSF-1, Kidney stone, 1,25(OH)₂D₃, Macrophage, Calcium oxalate

Fengbo Liu, Delin Yang, Chengxing Xia, Xiaofang Yang, Hang Yu, Pingxin Zhang, Zhipeng Li, Liufang Wang, Ju Li, Chunwei Ye. The role of colony-stimulating factor-1 and 1,25(OH)₂D₃ in macrophage proliferation and polarization and their impact on the formation of calcium oxalate kidney stones[J]. Chinese Journal of Endourology(Electronic Edition), 2026, 20(02): 202-208.

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References 27

[1]	Hill AJ, Basourakos SP, Lewicki P, et al. Incidence of kidney stones in the United States: the continuous national health and nutrition examination survey[J]. J Urol, 2022, 207(4): 851-856. DOI: 10.1097/JU.0000000000002331.
[2]	Sorokin I, Mamoulakis C, Miyazawa K, et al. Epidemiology of stone disease across the world[J]. World J Urol, 2017, 35(9): 1301-1320. DOI: 10.1007/s00345-017-2008-6.
[3]	Skolarikos A, Somani B, Neisius A, et al. Metabolic evaluation and recurrence prevention for urinary stone patients: an EAU guidelines update[J]. Eur Urol, 2024, 86(4): 343-363. DOI: 10.1016/j.eururo.2024.05.029.
[4]	Kusmartsev S, Dominguez-Gutierrez PR, Canales BK, et al. Calcium oxalate stone fragment and crystal phagocytosis by human macrophages[J]. J Urol, 2016, 195(4 Pt 1): 1143-1151. DOI: 10.1016/j.juro.2015.11.048.
[5]	俞国杰, 瓦热斯·先木西丁, 米尔扎提·麦麦提, 等. 复发性泌尿系结石成分变化及其影响因素分析[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(3): 259-265. DOI: 10.3877/cma.j.issn.1674-3253.2024.03.011.
[6]	Dardamanis M. Pathomechanisms of nephrolithiasis[J]. Hippokratia, 2013, 17(2): 100-107.
[7]	Arcidiacono T, Mingione A, Macrina L, et al. Idiopathic calcium nephrolithiasis: a review of pathogenic mechanisms in the light of genetic studies[J]. Am J Nephrol, 2014, 40(6): 499-506. DOI: 10.1159/000369833.
[8]	Grover PK, Thurgood LA, Fleming DE, et al. Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells[J]. Am J Physiol Renal Physiol, 2008, 294(2): F355-F361. DOI: 10.1152/ajprenal.00529.2007.
[9]	Taguchi K, Okada A, Kitamura H, et al. Colony-stimulating factor-1 signaling suppresses renal crystal formation[J]. J Am Soc Nephrol, 2014, 25(8): 1680-1697. DOI: 10.1681/ASN.2013060675.
[10]	Vervaet BA, Verhulst A, Dauwe SE, et al. An active renal crystal clearance mechanism in rat and man[J]. Kidney Int, 2009, 75(1): 41-51. DOI: 10.1038/ki.2008.450.
[11]	杨雄, 靳潇潇, 何文强. 巨噬细胞在草酸钙肾结石中的作用研究进展[J]. 现代免疫学, 2023, 43(4): 346-350. DOI: 1001-2478(2023)04-0346-05.
[12]	程帆. 泌尿系结石实验研究现状与展望[J]. 中华实验外科杂志, 2023, 40(6): 1013-1016. DOI: 10.3760/cma.j.cn421213-20221015-01315.
[13]	Ead JK, Armstrong DG. Granulocyte-macrophage colony-stimulating factor: Conductor of the wound healing orchestra? Int Wound J. 2023 Apr;20(4):1229-1234. DOI: 10.1111/iwj.13919. Epub 2023 Jan 12. PMID: 36632762; PMCID: PMC10031218.
[14]	Pixley FJ, Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action[J]. Trends Cell Biol, 2004, 14(11): 628-638. DOI: 10.1016/j.tcb.2004.09.016.
[15]	Stanley ER, Chen DM, Lin HS. Induction of macrophage production and proliferation by a purified colony stimulating factor[J]. Nature, 1978, 274(5667): 168-170. DOI: 10.1038/274168a0.
[16]	Zhu K, Gläser R, Mrowietz U. Vitamin D(3) and analogues modulate the expression of CSF-1 and its receptor in human dendritic cells[J]. Biochem Biophys Res Commun, 2002, 297(5): 1211-1217. DOI: 10.1016/s0006-291x(02)02357-4.
[17]	Holmes D. Stones: CSF-1 suppresses crystal formation[J]. Nat Rev Nephrol, 2014, 10(5): 242. DOI: 10.1038/nrneph.2014.46.
[18]	Riek AE, Oh J, Sprague JE, et al. Vitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic monocyte/macrophage phenotype in type 2 diabetic patients[J]. J Biol Chem, 2012, 287(46): 38482-38494. DOI: 10.1074/jbc.M112.386912.
[19]	刘权, 陶芝伟, 关晓峰, 等. 羟基磷灰石诱导巨噬细胞炎性反应及凋亡[J]. 中华实验外科杂志, 2017, 34(12): 2081-2083. DOI: 10.3760/cma.j.issn.1001-9030.2017.12.021.
[20]	拜合提亚尔·艾合买提江, 刘若天, 陈策, 等. Klotho基因敲降或过表达对乙醛酸盐诱导的小鼠肾结石模型的影响及机制研究[J]. 中华实验外科杂志, 2023, 40(6): 1034-1037. DOI: 10.3760/cma.j.cn421213-20220914-00669.
[21]	Bargagli M, Arena M, Naticchia A, et al. The role of diet in bone and mineral metabolism and secondary hyperparathyroidism[J]. Nutrients, 2021, 13(7): 2328. DOI: 10.3390/nu13072328.
[22]	Song Z, Guo Y, Zhou M, et al. The PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats[J]. Metabolism, 2014, 63(10): 1324-1333. DOI: 10.1016/j.metabol.2014.06.013.
[23]	Zhang XL, Guo YF, Song ZX, et al. Vitamin D prevents podocyte injury via regulation of macrophage M1/M2 phenotype in diabetic nephropathy rats[J]. Endocrinology, 2014, 155(12): 4939-4950. DOI: 10.1210/en.2014-1020.
[24]	Haussler MR, Whitfield GK, Kaneko I, et al. Molecular mechanisms of vitamin D action[J]. Calcif Tissue Int, 2013, 92(2): 77-98. DOI: 10.1007/s00223-012-9619-0.
[25]	李静玲, 柯坤彬, 王振丞, 等. CASR/VDR/PTH1R信号通路在含钙肾结石发生机制中的初步研究[J]. 昆明医科大学学报, 2022, 43(6): 13-18. DOI: 10.12259/j.issn.2095-610X.S20220609.
[26]	Tushinski RJ, Oliver IT, Guilbert LJ, et al. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy[J]. Cell, 1982, 28(1): 71-81. DOI: 10.1016/0092-8674(82)90376-2.
[27]	Guilbert LJ, Stanley ER. Specific interaction of murine colony-stimulating factor with mononuclear phagocytic cells[J]. J Cell Biol, 1980, 85(1): 153-159. DOI: 10.1083/jcb.85.1.153.

引物名称	引物方向	引物序列（5’→3’）	目的产物长度(bp)
CSF-1受体	正向	5’-GACCTCAACGAGCTCAAGGT-3’	501
CSF-1受体	反向	5’-GGTCTGGTGGCTGACTCCTA-3’	501
CD206	正向	5’-AGCAGGTGGTCAGTGGTTAG-3’	551
CD206	反向	5’-TCGATGATGAGGCTGTGAGT-3’	551
GAPDH	正向	5’-GAAGGTGAAGGTCGGAGTCA-3’	101
GAPDH	反向	5’-GACAAGCTTCCCGTTCTCAG-3’	101

引物名称	引物方向	引物序列（5’→3’）	目的产物长度(bp)
CSF-1受体	正向	5’-GACCTCAACGAGCTCAAGGT-3’	501
CSF-1受体	反向	5’-GGTCTGGTGGCTGACTCCTA-3’	501
CD206	正向	5’-AGCAGGTGGTCAGTGGTTAG-3’	551
CD206	反向	5’-TCGATGATGAGGCTGTGAGT-3’	551
GAPDH	正向	5’-GAAGGTGAAGGTCGGAGTCA-3’	101
GAPDH	反向	5’-GACAAGCTTCCCGTTCTCAG-3’	101

组别	CSF-1受体mRNA	CD206
对照组	1.01±0.09	1.01±0.14
CSF-1诱导组	3.36±0.51^**	4.26±0.67^**
1，25（OH）₂D₃₊CSF-1干预组	1.22±0.06^*	2.25±0.18^*

组别	CSF-1受体mRNA	CD206
对照组	1.01±0.09	1.01±0.14
CSF-1诱导组	3.36±0.51^**	4.26±0.67^**
1，25（OH）₂D₃₊CSF-1干预组	1.22±0.06^*	2.25±0.18^*

组别	0 d	6 d
对照组	2.03±0.19	2.04±0.19
CSF-1诱导组	2.03±0.19	2.15±0.23
1，25（OH）₂D₃₊CSF-1干预组	2.04±0.19	1.70±0.20

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The role of colony-stimulating factor-1 and 1,25(OH)₂D₃ in macrophage proliferation and polarization and their impact on the formation of calcium oxalate kidney stones

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